Age and dose sensitivities in the 2-butoxyethanol F344 rat model of hemolytic anemia and disseminated thrombosis.

Published

Journal Article

In hemolytic disorders, such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood. Appropriate animal models would increase the understanding of the pathophysiology of thrombosis. We previously reported that rats exposed to 2-butoxyethanol (2-BE) developed hemolytic anemia and disseminated thrombosis resembling sickle cell disease and beta-thalassemia. To characterize our model further, we investigated age- and dose-related differences in sensitivity to 2-BE. We exposed groups of 6- and 12-week-old F344 rats (5 animals/group) to 62.5, 125, and 250 mg/kg/day of 2-BE for up to 4 days. Blood was collected on days 2-4 for complete blood count and measurement of intracellular adhesion molecule-1 (ICAM-1). Histopathological evaluation was performed to find evidence of disseminated thrombosis. The maximum hemolytic response, resulting in decreased erythrocyte count and higher mean cell volume (MCV) occurred in the 12-week-old rats treated with the highest dose of 2-BE (250 mg/kg, p<0.0001). The highest increase in ICAM-1 levels occurred in the 12-week-old rats treated with 125 and 250 mg/kg 2-BE (p<0.0001). No intravascular thrombi were noted in the 6-week-old 2-BE-treated animals. The majority of intravascular thrombi occurred in the 12-week-old rats treated with 250 mg/kg 2-BE. Because our findings show age- and dose-related sensitivities, we suggest that 12-week-old rats and doses of 250 mg/kg be used in the 2-BE model.

Full Text

Duke Authors

Cited Authors

  • Ramot, Y; Lewis, DA; Ortel, TL; Streicker, M; Moser, G; Elmore, S; Ward, SM; Peddada, S; Nyska, A

Published Date

  • April 2007

Published In

Volume / Issue

  • 58 / 5

Start / End Page

  • 311 - 322

PubMed ID

  • 17261363

Pubmed Central ID

  • 17261363

Electronic International Standard Serial Number (EISSN)

  • 1618-1433

International Standard Serial Number (ISSN)

  • 0940-2993

Digital Object Identifier (DOI)

  • 10.1016/j.etp.2006.11.003

Language

  • eng